The Prostaglandin-Stroke Program is an interdisciplinary effort to broaden our understanding of the role of prostaglandins in the pathogenesis of thrombotic stroke and to enhance our knowledge concerning the use of prostaglandins in the prevention and treatment of stroke. Our major goal is to bring these basic investigations to clinical application in improved care of patients with stroke and allied disorders. The program contains seven interrelated projects. Projects 1 and 2 aim at the delineation of regulatory mechanisms for prostacyclin synthesis and stability. Serum factors involved in stimulation and stabilization of prostacyclin will be isolated and characterized. Their pathophysiologic significance will be systematically evaluated. Role of prostaglandins in plasminogen activator synthesis by cultured endothelial cells will be investigated. Projects 3 and 4 will study the roles of prostaglandins in modulating vascular wall connective tissue and basement membrane synthesis and degradation, and their role in platelet thrombus formation on damaged vessel wall. The effects of prostacyclin and selective thromboxane inhibitors or antagonists on thrombus formation and cerebral infarction will be determined by well-established animal models in projects 4 to 6. Moreover, Project 6 will address to some fundamental issues concerning the role of TXA2/PGH2 in initiation and sustaining platelet aggregation. Project 7 will investigate the chemistry of thromboxane synthetase and thromboxane A2. Thus, the scope of this program ranges from basic chemistry to clinical patient investigations and there exist an exciting potential for a rapid application of basic information to clinical management of stroke and vice versa. The program involves professional personnel with different backgrounds and expertise in hematology (coagulation and thrombosis), neurology, biochemistry, neurochemistry, neuropathology, enzymology, pharmacology, tissue culture, RIA's, medicinal chemistry, and connective tissue biochemistry. It is intended that this program will enable several laboratories to work individually and together to achieve the highest degree of innovation and productivity.